From Production of Peptides in Milligram Amounts for Research to Multi-Tons Quantities for Drugs of the Future

University of Barcelona, Barcino, Catalonia, Spain
Current Pharmaceutical Biotechnology (Impact Factor: 2.51). 03/2004; 5(1):29-43. DOI: 10.2174/1389201043489620
Source: PubMed


Peptides are key to modern drug discovery. This article reviews the requirements for bulk production of peptides and how it affects research and production of smaller scales. Peptides, as modern drugs, are currently produced in millions in mg-scale for research purpose, in order to better understand the function of biological systems. Some newly discovered sequences form the basis of modern drugs and are now produced in multi-tons. The most popular example is the T-20 peptide (Fuzeon), which is the first peptide produced at such scale by a combination of solid phase and solution phase methodologies. This particular peptide sequence has the ability to dock on the surface of the HIV virus and block the virus from entering into a human blood cell, helping patient life conditions. A multi-ton scale production was made necessary based on the high number of patients, the socio-economical importance of the disease and the strong support by governmental institutions such as the FDA. Fuzeon is the first peptide-based drug that is produced in multi-tons on solid support. This had revolutionary effects on the whole peptide synthesis techniques in general including the production of the starting materials. It also had a positive impact on the cost-effectiveness of peptides for research, as the standard technique for producing peptides in research quantities is solid phase chemistry. The decrease of the cost of all starting materials will lead to an increase of the number of produced peptides, which will certainly bring new interesting and effective sequences to be used as novel drugs.

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    • "There are now several dozen peptide therapeutics approved for clinical use and the market for therapeutics peptides is estimated to reach $11.5billion by 2013 (BioNest). Over the last decade or so, processes in peptide manufacture have considerably evolved, partly due to the experience of scaling up production from milligram to multi-ton levels [143,144]). These requirements have generated important improvements in both technical and cost efficiency aspects of process design, manufacturing capacity and peptide synthesis [145]. "
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    • "*, **, and *** mean P < 0.05, P < 0.01, and P < 0.001, respectively. (Bruckdorfer et al., 2004; Park et al., 2009). Synthetic combinatorial peptide libraries have been utilized successfully to discover bioactive peptides such as antimicrobial peptides (Blondelle et al., 1996), ligands for cell surface receptors (Bae et al., 2003), protein kinase inhibitors and substrates (Wu et al., 1994; Songyang et al., 1995), and peptide mimotopes of receptor binding sites (Bracci et al., 2001). "
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